Marleen van der Laan
Groningen University
Narrative cv coming soon
Presentation: Targeting the host heat shock protein 70 machinery to inhibit chikungunya virus replication
Abstract: The growing threat of emerging and re-emerging viral infections highlights the need for effective antiviral strategies. Viruses are obligate intracellular parasites that depend entirely on the host cell, presenting a key vulnerability in the viral replication cycle. Host cellular factors and pathways essential for viral replication can therefore serve as antiviral targets, offering broad-spectrum potential by exploiting shared dependencies across multiple viruses. Unlike traditional antivirals, which can lead to resistance, host-directed approaches provide a promising alternative with a reduced likelihood of resistance development, as the targets are not under viral genetic control. In this study, we investigated the molecular virus-host interactions during chikungunya virus (CHIKV) infection to identify critical host factors required for viral replication. We demonstrated that CHIKV hijacks the host molecular chaperone machinery, specifically Heat shock protein 70s (Hsp70s), to produce infectious progeny. Using allosteric Hsp70 inhibitors, we showed that pharmacological inhibition of this molecular chaperone significantly impairs CHIKV replication in vitro and ex vivo, establishing proof-of-concept for targeting host chaperones as an antiviral strategy. These findings provide functional insights into CHIKV replication and host dependencies and support further exploration of Hsp70 inhibitors as a host-directed therapeutic approach to combat CHIKV.
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